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A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Mavrilimumab (KPL-301) Treatment in Adult Subjects Hospitalized With Severe COVID-19 Pneumonia and Hyper-inflammation

Trial Profile

A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Mavrilimumab (KPL-301) Treatment in Adult Subjects Hospitalized With Severe COVID-19 Pneumonia and Hyper-inflammation

Status: Recruiting
Phase of Trial: Phase II/III

Latest Information Update: 08 Jun 2021

At a glance

  • Drugs Mavrilimumab (Primary)
  • Indications COVID-19 pneumonia; Inflammation; Respiratory insufficiency
  • Focus Registrational; Therapeutic Use
  • Sponsors Kiniksa Pharmaceuticals
  • Most Recent Events

    • 08 Jun 2021 According to a Kiniksa Pharmaceuticals media release, Phase 3 portion of this trial has already enrolled over 400 patients and is currently enrolling patients; data from this Phase 3 portion is expected in the first quarter of 2022.
    • 08 Jun 2021 According to a Kiniksa Pharmaceuticals media release, based upon data from the Phase 2 portion of this trial and discussions with the FDA, Kiniksa has adjusted the final sample size to appropriately power the Phase 3 portion of the clinical trial. the Phase 3 clinical trial will enroll a total of approximately 600 non-mechanically ventilated patients..
    • 12 Apr 2021 According to a Kiniksa Pharmaceuticals media release, the company continues to enroll patients in the Phase 3 portion of this trial, which has already enrolled over 250 patients.

Trial Overview

Outcome

Primary endpoint met - positive

Purpose

This Phase II/III trial will evaluate Mavrilimumab for the treatment of patients with COVID-19 pneumonia and hyperinflammation.

Kiniksa's Phase 2/3 clinical trial protocol is a global, randomized, double-blind, placebo-controlled study encompassing 2 phases of development (Phase 2 and Phase 3).

The Phase 2 portion of the trial is expected to enroll approximately 160 patients and is intended to evaluate the efficacy and safety of 2 dose levels of mavrilimumab relative to placebo in patients who have tested positive for COVID-19 and have x-ray/CT evidence of bilateral pneumonia, active or recent fever, and clinical laboratory results indicative of hyper inflammation.

The Phase 3 portion is expected to enroll approximately 420 patients and is intended to confirm Phase 2 efficacy and safety findings. In both Phase 2 and Phase 3, patients are expected to be enrolled into 2 cohorts: Cohort 1 will include non-intubated, hospitalized patients who require supplemental oxygen to maintain SpO2 = 92%, (i.e., non-mechanically ventilated patients); and Cohort 2 will include hospitalized patients for whom mechanical ventilation was recently initiated within 48 hours prior to randomization (i.e., ventilated patients).

Following screening, enrolled patients in each cohort will be randomized 1:1:1 to receive a single IV infusion of mavrilimumab 6mg/kg or 10 mg/kg or placebo (Day 1). The primary efficacy endpoint for the Phase 2 portion of the trial for Cohort 1 is the proportion of patients alive and without respiratory failure (defined as the need for high flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation) at Day 15 and for Cohort 2 is the mortality rate by Day 15.

There will be a seamless transition in enrollment of patients in both cohorts between the Phase 2 and Phase 3 portions of the trial. For each cohort, once the last patient in Phase 2 is enrolled, all subsequent patients will be considered Phase 3 patients. Once the last patient in Phase 2 completes Day 15, primary efficacy and safety analyses of the Phase 2 data will be conducted. Following demonstration of efficacy and safety in Phase 2, the Phase 3 portion of the trial will be continued/completed

Primary Endpoints

Met on 12 Apr 2021

Cohort 1: Proportion of Participants Alive and Free of Mechanical Ventilation at Day 29

description: Mechanical ventilation is defined as invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO).
time_frame: Day 29 [1]

Cohort 2: Mortality Rate at Day 29

description: Mortality rate is defined as the proportion of participants who have died by Day 29.
time_frame: Day 29

Other Endpoints

Cohort 1: Time to 2-point clinical Improvement by Day 29

description: Defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. Participants who die before Day 29 will be censored at Day 30.
The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.
time_frame: By Day 29

Cohort 1: Time to return to room air or discharge by Day 29

description: Defined as time from randomization to the start date of breathing room air (NIAID score ≥ 5), or discharge from the hospital, whichever occurs first. Participants who die before Day 29 will be censored at Day 30.
time_frame: By Day 29

Cohort 1: Mortality rate at Day 29

description: Mortality rate is defined as the proportion of participants who die.
time_frame: Day 29

Cohort 2: Time to 1-point clinical improvement by Day 29

description: Defined as time from randomization to a 1-point improvement on the NIAID 8-point ordinal scale, or discharge from the hospital, whichever comes first. Subjects who die before Day 29 will be censored at Day 30.
time_frame: By Day 29 [2]

Diseases Treated

Indication Qualifiers Patient Segments
COVID-19 pneumonia treatment severe
Inflammation treatment -
Respiratory insufficiency prevention -

Subjects

  • Subject Type patients
  • Number

    Planned: 588

  • Sex male & female
  • Age Group ≥ 18 years; adult

Patient Inclusion Criteria

Key - Subject (or legally authorized representative) is able and willing to provide informed consent, which includes compliance with study requirements and restrictions listed in the consent form - Positive SARS-CoV-2 (2019-nCoV) test within 14 days prior to randomization - Hospitalized for SARS-CoV-2 - Bilateral pneumonia on chest x-ray or computed tomography - Clinical laboratory results indicative of hyper-inflammation - Cohort 1: Receiving any form of oxygenation or NIV to maintain SpO2 ≥ 92% and not-intubated (examples include nasal cannula, face mask, venturi mask, high-flow nasal cannula, or non-invasive positive pressure ventilation) - Cohort 2: Recently ventilated with mechanical ventilation prior to randomization Key

Patient Exclusion Criteria

- Onset of COVID-19 symptoms or positive COVID-19 test result > 14 days prior to randomization - Hospitalized > 7 days prior to randomization - Need for invasive mechanical ventilation (Only for Cohort 1) - Need for ECMO - Serious prior or concomitant illness that in the opinion of the Investigator precludes the subject from enrolling in the trial - Recent treatment with cell-depleting biological therapies (eg, anti-CD20) within 12 months, non-cell-depleting biological therapies (such as anti-tumor necrosis factor [TNF], anakinra, anti-IL-6 receptor [eg, tocilizumab], or abatacept) within 8 weeks (or 5 half-lives, whichever is longer), treatment with alkylating agents within 12 weeks, treatment with cyclosporine A, azathioprine, cyclophosphamide, mycophenolate mofetil (MMF), or other immunosuppressant (except for corticosteroids) within 4 weeks prior to randomization - Corrected QT interval Fridericia's formula (QTcF) on Screening electrocardiogram (ECG) ≥500 ms - Enrolled in another investigational study of a medical intervention - Life expectancy less than 48 hours - Known human immunodeficiency virus infection (regardless of immunological status), known hepatitis B virus surface antigen positivity and/or anti-hepatitis C virus positivity

Trial Details

Identifiers

Identifier Owner
NCT04447469 ClinicalTrials.gov: US National Institutes of Health
KPL301C203 -

Organisations

  • Sponsors Kiniksa Pharmaceuticals
  • Affiliations Kiniksa Pharmaceuticals

Trial Dates

  • Initiation Dates

    Planned : 01 Jul 2020

    Actual : 27 Jul 2020

  • Primary Completion Dates

    Planned : 01 Dec 2021

  • End Dates

    Planned : 01 Feb 2022

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised
  • Phase of Trial Phase II/III
  • Location Brazil; Chile; Peru; South Africa; USA
  • Focus Registrational; Therapeutic Use

Interventions

Drugs Route Formulation
MavrilimumabPrimary Drug Intravenous Infusion

10 mg/kg (Cohort 1)

Non-mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion
Drug: mavrilimumab (anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4])) Other Name: (KPL-301; CAM3001)

10 mg/kg (Cohort 2)

Mechanically ventilated participants administered mavrilimumab 10 mg/kg as a single IV infusion
Drug: mavrilimumab (anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4])) Other Name: (KPL-301; CAM3001)

6 mg/kg (Cohort 1)

Non-mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion
Drug: mavrilimumab (anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4])) Other Name: (KPL-301; CAM3001)

6 mg/kg (Cohort 2)

Mechanically ventilated participants administered mavrilimumab 6 mg/kg as a single IV infusion
Drug: mavrilimumab (anti-granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSF-Rα) monoclonal antibody (human isoform immunoglobulin G [IgG4])) Other Name: (KPL-301; CAM3001)

Placebo (Cohort 1)

Non-mechanically ventilated participants administered placebo as a single IV infusion
Other: Placebo (matching placebo)

Placebo (Cohort 2)

Mechanically ventilated participants administered placebo as a single IV infusion
Other: Placebo (matching placebo)

Results

Therapeutic efficacy

In phase II/III study, mavrilimumab achieved primary efficacy endpoint of the proportion of patients alive and free of mechanical ventilation at Day 29. 12.3% points higher proportion of patients alive and free of mechanical ventilation in mavrilimumab (86.7%) compared with placebo (74.4%) (p=0.1224 met predefined statistical threshold of p<0.2) was observed. Patients receiving mavrilimumab demonstrated 65% reduction in in the risk of mechanical ventilation or death through Day 29 (Hazard Ratio (HR) = 0.35; p=0.0175). At day 29, 12.5% lower mortality was observed in patients receiving mavrilimumab (8%) compared with placebo recipients (20.5%) (p=0.0718). Reduction in risk of death at day 29 was 61% in mavrilimumab receiving patients (HR= 0.39; p=0.0726). Differences were not observed in the 10 mg/kg and 6mg/kg IV treatment arms. Clinical improvement was observed on top of steroids and/or antivirals [1] .

Adverse events

In phase II/III, mavrilimumab was well tolerated and demonstrated favorable safety profile. In placebo group, single treatment-emergent serious adverse event related to study drug was reported. Notable dose-related adverse events were not observed. In all groups including placebo, infections were observed and thrombotic events were observed in only placebo recipients [1] .

Publications

  1. Kiniksa Pharmaceuticals. Kiniksa Announces Positive Results for Mavrilimumab Phase 2 Trial in Non-Mechanically Ventilated Severe COVID-19 Patients. Media-Rel 2021;.

    Media Release

Authors

Author Total Publications First Author Last Author
Kiniksa Pharmaceuticals 1 1 1

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Kiniksa Clinical Research Team
(781) 431-9100 clinicaltrials@kiniksa.com
show details
-

Centres

Centre Name Location Trial Centre Country
-
-
-
Affinity Health Oak Brook, Illinois USA
Allina Health System Minneapolis, Minnesota USA
Bryn Mawr Bryn Mawr, Pennsylvania USA
Centro de Pesquisas Clínicas Natal Brazil
Clinica Las Condes Santiago Chile
Clinica Providencia San Miguel Peru
Clinica Providencia Santiago Chile
Essalud - Hospital de Emergencias Grau Lima Cercado Peru
Fundação Faculdade Regional de Medicina de São José do Rio Preto São José Brazil
Hospital Adventista de Belem Belém Brazil
Hospital Alemão Oswaldo Cruz São Paulo Brazil
Hospital Bruno Born Lajeado Brazil
Hospital Cardio Pulmonar Salvador Brazil
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo Ribeirão Preto Brazil
Hospital Essalud Alberto Sabogal Sologuren Bellavista Peru
Hospital Nacional Cayetano Heredia San Martín De Porres Peru
IATROS International Bloemfontein South-Africa
IEP HGF - Instituto de Estudos e Pesquisas Clinicas do Ceará Fortaleza Brazil
Instituto Mário Penna Belo Horizonte Brazil
Into Research - Little Company of Mary Medical Center Pretoria South-Africa
IPECC - Instituto de Pesquisa Clínica de Campinas Campinas Brazil
Kiniksa Pharmaceuticals, Ltd.
-
-
Limpopo Clinical Research Initiative Rustenburg South-Africa
Mercy Hospital Springfield, Missouri USA
Sharp Health Care San Diego, California USA
TASK Eden George South-Africa
Tiervlei Trial Center Cape Town South-Africa
Tulane Medical Center New Orleans, Louisiana USA
UCLA Medical Center Los Angeles, California USA
University of Cincinnati Cincinnati, Ohio USA
University of Texas Health Sciences Houston, Texas USA
UPECLIN - Unidade de Pesquisa Clínica Botucatu Brazil

Trial History

Event Date Event Type Comment
08 Jun 2021 Other trial event According to a Kiniksa Pharmaceuticals media release, Phase 3 portion of this trial has already enrolled over 400 patients and is currently enrolling patients; data from this Phase 3 portion is expected in the first quarter of 2022. Updated 14 Jun 2021
08 Jun 2021 Other trial event According to a Kiniksa Pharmaceuticals media release, based upon data from the Phase 2 portion of this trial and discussions with the FDA, Kiniksa has adjusted the final sample size to appropriately power the Phase 3 portion of the clinical trial. the Phase 3 clinical trial will enroll a total of approximately 600 non-mechanically ventilated patients.. Updated 14 Jun 2021
12 Apr 2021 Other trial event According to a Kiniksa Pharmaceuticals media release, the company continues to enroll patients in the Phase 3 portion of this trial, which has already enrolled over 250 patients. Updated 22 May 2021
12 Apr 2021 Endpoint met Primary endpoint of proportion of Participants Alive and Free of Mechanical Ventilation at Day 29 has been met, according to a Kiniksa Pharmaceuticals media release. Updated 22 May 2021
12 Apr 2021 Results Results presented in a Kiniksa Pharmaceuticals media release. Updated 22 May 2021
11 Mar 2021 Other trial event Last checked against ClinicalTrials.gov record. Updated 11 Mar 2021
05 Mar 2021 Other trial event Planned number of patients changed from 580 to 588. Updated 11 Mar 2021
05 Mar 2021 Completion date Planned End Date changed from 1 Apr 2021 to 1 Feb 2022. Updated 11 Mar 2021
05 Mar 2021 Other trial event Planned primary completion date changed from 1 Feb 2021 to 1 Dec 2021. Updated 11 Mar 2021
23 Feb 2021 Other trial event According to a Kiniksa Pharmaceuticals media release, the company completed enrollment in the Phase 2 portion of the trial and is enrolling patients in the Phase 3 portion. Updated 25 Feb 2021
22 Dec 2020 Other trial event According to a Kiniksa Pharmaceuticals media release, data from the phase 2 portion of this study is expected in the first half of 2021. Updated 31 Dec 2020
06 Oct 2020 Other trial event According to a Kiniksa Pharmaceuticals media release, the company is enrolling the Phase 2 portion of a global, randomized, double-blind, placebo-controlled adaptive design Phase 2/3 clinical trial. Updated 13 Oct 2020
19 Jul 2020 Other trial event Planned initiation date changed from 1 Jun 2020 to 1 Jul 2020. Updated 22 Jul 2020
19 Jul 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 22 Jul 2020
29 Jun 2020 Other trial event New source identified and integrated ClinicalTrials.gov: (US National Institutes of Health: NCT04447469) Updated 22 Jul 2020
24 Jun 2020 Status change - not yet recruiting Status changed from planning to not yet recruiting. Updated 29 Jun 2020
08 Jun 2020 Other trial event According to a Kiniksa Pharmaceuticals media release, the company announced an active investigational new drug application (IND) with the U.S. Food and Drug Administration (FDA) for this trial. Updated 10 Jun 2020
07 Apr 2020 New trial record New trial record Updated 07 Apr 2020
31 Mar 2020 Other trial event According to a Kiniksa Pharmaceuticals media release, the company is engaging with the U.S. Food and Drug Administration (FDA) regarding the path forward for potential Phase 2/3 clinical development of mavrilimumab in COVID-19 pneumonia. Updated 07 Apr 2020

References

  1. Kiniksa Pharmaceuticals. Kiniksa Announces Positive Results for Mavrilimumab Phase 2 Trial in Non-Mechanically Ventilated Severe COVID-19 Patients. Media-Rel 2021;.

    Media Release
  2. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2021;.

    Available from: URL: http://clinicaltrials.gov
  3. Kiniksa Pharmaceuticals. Kiniksa Outlines Next Steps for the Development of Mavrilimumab. Media-Rel 2021;.

    Media Release
  4. Kiniksa Pharmaceuticals. Kiniksa Announces Early Evidence of Treatment Response with Mavrilimumab in 6 Patients with Severe COVID-19 Pneumonia and Hyperinflammation. Media-Rel 2020;.

    Media Release
  5. Kiniksa Pharmaceuticals. Kiniksa Reports Fourth Quarter and Full-Year 2020 Financial Results and Corporate and Pipeline Activity. Media-Rel 2021;.

    Media Release
  6. Kiniksa Pharmaceuticals. Kiniksa Announces Data from U.S. Investigator-Initiated Study of Mavrilimumab in Severe COVID-19 Pneumonia and Hyperinflammation. Media-Rel 2020;.

    Media Release
  7. Kiniksa Pharmaceuticals. Kiniksa Reports First Quarter 2020 Financial Results and Highlights Recent Corporate and Pipeline Activity. Media-Rel 2020;.

    Media Release
  8. Kiniksa Pharmaceuticals. Kiniksa Announces 28-Day Clinical Outcomes Data from Mavrilimumab Treatment Protocol in Severe COVID-19 Pneumonia and Active U.S. IND for Phase 2/3 Clinical Trial. Media-Rel 2020;.

    Media Release
  9. Kiniksa Pharmaceuticals. Kiniksa Announces Positive Data from Phase 2 Trial of Mavrilimumab in Giant Cell Arteritis. Media-Rel 2020;.

    Media Release
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